Lactase persistence and milk consumption as determinants of ovarian cancer risk

Using published data, largely from the 1970s, the author compared ovarian cancer incidence, per capita milk consumption, and population estimates of lactase persistence (the ability to digest lactose after infancy) in 27 countries. Significant positive correlations were noted between ovarian cancer incidence, per capita milk consumption, and lactase persistence. Lactase persistence showed a stronger association than milk consumption or animal fat consumption in multiple regression models. The author speculates that toxicity from the lactose component of milk and, more specifically, galactose, the digestion of which is facilitated by lactase persistence, may provide a biologic basis for the correlation.     

Association of dairy products,lactose, and calcium with the risk of ovarian cancer

Epidemiologic findings have been inconsistent regarding the association of dietary fat, dairy products, and lactose with risk of ovarian cancer. The authors conducted a case-control study in Hawaii and Los Angeles, California, to examine several dietary hypotheses regarding the etiology of ovarian cancer in a population with a broad range of dietary intakes. A total of 558 patients with ovarian cancer diagnosed in 1993-1999 and 607 controls were interviewed regarding their diet. Consumption of all dairy products, all types of milk, and low-fat milk, but not consumption of whole milk, was significantly inversely related to the odds of ovarian cancer. Similar inverse gradients in the odds ratios were obtained for intakes of lactose and calcium, although these nutrients were highly correlated (r = 0.77). The odds ratio for ovarian cancer was 0.46 (95% confidence interval: 0.27, 0.76) among women in the highest quartile of dietary calcium intake versus the lowest (p for trend = 0.0006). The significant dietary association was limited to dairy sources of calcium (p for trend = 0.003), although a nonsignificant inverse gradient in risk was also found in relation to calcium supplement intake. These results suggest that intake of low-fat milk, calcium, or lactose may reduce the risk of ovarian cancer.     

A case-control study of milk-drinking and ovarian cancer risk

It has been hypothesized that milk consumption increases the risk of ovarian cancer because of a possible association of lactose with human ovarian failure. Milk is also a source of animal fats in the diet, and animal fat intake is associated with ovarian cancer risk. To explore further the possible confounding of the milk-ovarian cancer association by the animal fat content of milk, the authors performed a case-control study of 303 ovarian cancer cases and 606 age-matched nonmalignant-disease controls seen between 1982 and 1988 at Roswell Park Memorial Institute in Buffalo, New York. Total frequency of usual milk intake was not associated with increased risk. Usually drinking more than one glass of whole milk daily relative to never drinking whole milk was associated with a relative risk of 3.1 (95% confidence interval (CI) 1.8-5.5). Consumption of reduced-fat milk was associated with reduced relative risk. Among persons who reported drinking milk regularly, persons reporting drinking only whole milk were at increased risk (relative risk = 2.6, 95% CI 1.7-4.0) relative to persons who drank only skim milk or 2% milk. These findings suggest that milk-drinking is not a source of ovarian cancer risk independently of its fat content. Additional study of lactose and ovarian cancer risk involving careful control for confounding is needed.     

Lactose absorption in patients with ovarian cancer.

To determine whether lactase persistence might be related to ovarian cancer risk, in 1994-1995 the authors assessed the capacity to digest lactose by measuring breath hydrogen production after oral administration of lactose in 50 women with ovarian cancer and 100 healthy controls. All of the women came from Sassari (Sardinia), Italy, an area where the population has a high frequency of lactose malabsorption. Thirty percent of cases were lactose absorbers, as compared with 15% of controls. The odds ratio for ovarian cancer among lactose absorbers was 2.51 (95% confidence interval 1.10-5.68). These results provide some support for a role of lactose ingestion and galactose cytotoxicity in the pathogenesis of ovarian cancer.     

High prevalence of lactose absorbers in Northern Sardinian patients with type 1 and type 2 diabetes mellitus

BACKGROUND: Increased intestinal lactase activity has been shown to occur in alloxan and streptozotocin diabetic rats. OBJECTIVE: The objective of this study was to determine whether increased intestinal lactase activity is present in humans with diabetes mellitus. DESIGN: We assessed the capacity to digest lactose by measuring breath-hydrogen production after oral administration of lactose in 50 patients with type 1 diabetes, 50 patients with type 2 diabetes, and 50 healthy control subjects from Sassari, Sardinia, Italy, a population characterized by a low prevalence of lactase persistence (lactose absorbers). RESULTS: Fourteen percent of control subjects were lactose absorbers, compared with 48% of patients with type 1 diabetes and 52% of patients with type 2 diabetes (P < 0.005). The odds ratio of lactase persistence in patients with type 1 diabetes was 5.3 (95% CI: 2.0, 14.0) and in patients with type 2 diabetes was 5.5 (95% CI: 2.1, 14.5). CONCLUSIONS: Diabetes is associated with increased intestinal lactase activity in humans. Consequently, there is a greater exposure to glucose and galactose in diabetic patients with high lactose consumption. This may explain the association between diabetes and the risk of cataract.     

Relationship between calcium, lactose, vitamin D, and dairy products and ovarian cancer

Few prospective studies of the relationship between intake of dairy foods, calcium, vitamin D, and lactose and ovarian cancer have been conducted, and results have been largely inconsistent. Two recent studies found significant increased risk with frequent dairy consumption and perhaps with high intakes of calcium or lactose. The authors investigated the association between these foods and nutrients and ovarian cancer risk among 31,925 subjects in the Breast Cancer Detection Demonstration Project follow-up cohort. Multivariable (MV) relative risks (RRs) adjusted for age, parity, and other factors were estimated using Cox proportional hazards models. Over an average follow-up of 8.3 yr, 146 incident ovarian cancer cases were confirmed. Higher intakes of total dairy food (comparing four or more servings per day vs. less than one serving per day) were associated with a statistically significant decreased risk of ovarian cancer, although the trend was not significant (MV RR = 0.42; 95% confidence interval (CI) = 0.20-0.89; P for trend = 0.07). Comparing extreme quartiles, we observed a statistically nonsignificant inverse association between high dietary calcium intake and ovarian cancer (RR = 0.67; 95% CI = 0.43, 1.04; P for trend = 0.08). No statistically significant relations were found for consumption of specific dairy foods, lactose, or vitamin D and ovarian cancer risk. The possibility of a decreased risk of ovarian cancer for dietary calcium merits further evaluation.     

Dietary fat intake and risk of epithelial ovarian cancer: a meta-analysis of 6,689 subjects from 8 observational studies

The etiology of epithelial ovarian cancer is unknown. Prior work suggests that high dietary fat intake is associated with an increased risk of this tumor, although this association remains speculative. A meta-analysis was performed to evaluate this suspected relationship. Using previously described methods, a protocol was developed for a meta-analysis examining the association between high vs. low dietary fat intake and the risk of epithelial ovarian cancer. Literature search techniques, study inclusion criteria, and statistical procedures were prospectively defined. Data from observational studies were pooled using a general variance-based meta-analytic method employing confidence intervals (CI) previously described by Greenland. The outcome of interest was a summary relative risk (RRs) reflecting the risk of ovarian cancer associated with high vs. low dietary fat intake. Sensitivity analyses were performed when necessary to evaluate any observed statistical heterogeneity. The literature search yielded 8 observational studies enrolling 6,689 subjects. Data were stratified into three dietary fat intake categories: total fat, animal fat, and saturated fat. Initial tests for statistical homogeneity demonstrated that hospital-based studies accounted for observed heterogeneity possibly because of selection bias. Accounting for this, an RRs was calculated for high vs. low total fat intake, yielding a value of 1.24 (95% CI = 1.07-1.43), a statistically significant result. That is, high total fat intake is associated with a 24% increased risk of ovarian cancer development. The RRs for high saturated fat intake was 1.20 (95% CI = 1.04-1.39), suggesting a 20% increased risk of ovarian cancer among subjects with these dietary habits. High vs. low animal fat diet gave an RRs of 1.70 (95% CI = 1.43-2.03), consistent with a statistically significant 70% increased ovarian cancer risk. High dietary fat intake appears to represent a significant risk factor for the development of ovarian cancer. The magnitude of this risk associated with total fat and saturated fat is rather modest. Ovarian cancer risk associated with high animal fat intake appears significantly greater than that associated with the other types of fat intake studied, although this requires confirmation via larger analyses. Further work is needed to clarify factors that may modify the effects of dietary fat in vivo.     

The Globalization of Cow's Milk Production and Consumption: Biocultural Perspectives

Cow's milk consumption has been relatively rare in human history, largely confined to populations with genetic adaptations for continued production of lactase, the enzyme that breaks down the unique milk sugar lactose. But in the last forty years, both the production and consumption of cow's milk have spread around the world, and trade in milk products has likewise increased. Populations with no history of milk drinking have embraced this new beverage, and governments promote its consumption in their food-based dietary guidelines and school milk programs. China is a particularly good example of this trend. There the dairy industry is growing rapidly and milk consumption has become increasingly common in urban areas. Milk is viewed as especially appropriate for children, with growth-promoting properties; the larger size and athletic success of western athletes is often attributed to their greater milk consumption.

Milk is a very unusual food insofar as it is uniquely produced by mammals to support the growth, maturation, and health of nursing infants. Furthermore, there is variation among human populations with respect to the production of lactase in adulthood (lactase persistence/impersistence); consumption of lactose, which is only found in milk, beyond the traditional nursing period can result in the gastrointestinal symptoms of lactose intolerance. Thus the surge in consumption among lactase impersistent populations is likely to be accompanied by increases in digestive complaints. With regard to the purported positive relationship between milk and growth, the current evidence is not compelling that milk consumption in childhood results in significant gains in height.     

Dietary Fat Intake and Risk of Ovarian Cancer: A Systematic Review and Dose–Response Meta-Analysis of Observational Studies

Observational studies have reported controversial evidence of the association between dietary fat intake and ovarian cancer. This dose–response meta-analysis aimed to clarify quantitatively the association between dietary fat intake and ovarian cancer. The linear and non-linear relationships between fat intake and risk of ovarian cancer were investigated. Heterogeneity, sensitivity analysis, and publication bias were also assessed. Overall, 21 studies involved approximately 900,000 subjects were included. A significant nonlinear association was found between total fat intake with the risk of ovarian cancer, with a relatively steep slope at total fat intake higher than 30?g/day (p non-linearity <.01). Moreover, the risk of ovarian cancer was increased in non-linear form for both saturated and monounsaturated fat from 25?g/day (p non-linearity <.05). According to the findings from the linear meta-analysis, we observed a 2, 2, 1, and 1% greater risk of ovarian cancer per 10, 0.5, 2.5?g/day and 50?mg/day increase in total, trans and monounsaturated fat intake as well as cholesterol, respectively. However, this association for monounsaturated fat was marginally significant (p=.052). The findings of this meta-analysis suggest that dietary total, trans, saturated and partially monounsaturated fat as well as cholesterol intake are positively associated with increased risk of ovarian cancer.     

Allaying Fears and Fallacies about Lactose Intolerance

Public awareness and misunderstandings of lactose intolerance are at an all-time high. Many people erroneously believe they are lactose intolerant or develop gastrointestinal symptoms after intake of lactose. Consequently, lactose-containing foods such as milk and other dairy foods may be eliminated unnecessarily from the diet. Because these foods are a major source of calcium, low intake of them can compromise calcium nutriture. This, in turn, can increase the risk of major chronic diseases such as osteoporosis (porous bones) and hypertension. This review is intended to help dietetics professionals alleviate clients' fears about lactose intolerance and recommend dietary strategies to improve tolerance to lactose. Scientific findings indicate that the prevalence of lactose intolerance is grossly overestimated. Other physiologic and psychologic factors can contribute to gastrointestinal symptoms that mimic lactose intolerance. Scientific findings also indicate that people with laboratory-confirmed low levels of the enzyme lactase can consume 1 serving of milk with a meal or 2 servings of milk per day in divided doses at breakfast and dinner without experiencing symptoms. Several dietary strategies are available to help lactose maldigesters include milk and other dairy foods in their diet without experiencing symptoms. J Am Diet Assoc. 1998;98:671-676.     

Milk and lactose intakes and ovarian cancer risk in the Swedish Mammography Cohort

BACKGROUND: High intakes of dairy products and of the milk sugar lactose have been hypothesized to increase ovarian cancer risk, but prospective data are scarce. OBJECTIVE: We examined the association between intakes of dairy products and lactose and the risk of total epithelial ovarian cancer and its subtypes. DESIGN: This was a prospective population-based cohort study of 61 084 women aged 38-76 y who were enrolled in the Swedish Mammography Cohort. Diet was assessed in 1987-1990 with the use of a self-administered food-frequency questionnaire. During an average follow-up of 13.5 y, 266 women were diagnosed with invasive epithelial ovarian cancer; 125 of those women had serous ovarian cancer. RESULTS: After adjustment for potential confounders, women who consumed >/=4 servings of total dairy products/d had a risk of serous ovarian cancer (rate ratio: 2.0; 95% CI: 1.1, 3.7; P for trend = 0.06) twice that of women who consumed <2 servings/d. No significant association was found for other subtypes of ovarian cancer. Milk was the dairy product with the strongest positive association with serous ovarian cancer (rate ratio comparing consuming >/=2 glasses milk/d with consuming milk never or seldom: 2.0; 95% CI: 1.1, 3.7; P for trend = 0.04). We observed a positive association between lactose intake and serous ovarian cancer risk (P for trend = 0.006). CONCLUSIONS: Our data indicate that high intakes of lactose and dairy products, particularly milk, are associated with an increased risk of serous ovarian cancer but not of other subtypes of ovarian cancer. Future studies should consider ovarian cancer subtypes separately.     

Prospective study on milk products, calcium and cancers of the colon and rectum

OBJECTIVE: To study the relationship between consumption of milk and milk products, calcium, lactose and vitamin D and occurrence of colorectal cancers. DESIGN: Prospective cohort study. SUBJECTS: A total of 9959 men and women aged 15 y or older without history of cancer at baseline. During a 24 y follow-up, 72 new cancers of the large bowel (38 in the colon and 34 in the rectum) were detected. RESULTS: Consumption of milk and total milk products was suggested to be inversely related to colon cancer incidence, whereas no similar association was seen for rectal cancer. The relative risk between the highest and lowest quartiles of intake adjusted for potential confounding factors was 0.46 (95% confidence interval 0.14-1.46, P for trend 0.09) for milk and 0.37 (95% CI=0.12-1.39, P for trend 0.06) for total milk products. Lactose intake showed a similar inverse relationship with colon cancer: the relative risk was 0.31 (95% CI=0.08-1.15, P for trend 0.03). Intake of vitamin D or total dietary calcium was not significantly related to colorectal cancer risk, whereas calcium provided by fermented milk products was associated with increased colorectal cancer incidence; in the highest quartile the multivariate adjusted relative risk for colorectal cancer was 2.07 (95% CI=1.00-4.28). CONCLUSIONS: Our results indicate that individuals showing high consumption of milk have a potentially reduced risk of colon cancer; however, the association does not appear to be due to intake of calcium, vitamin D, or to specific effects of fermented milk. SPONSORSHIP: This study was supported by a grant from the Swedish Cancer Foundation.     

Lactase persistence,milk intake,and mortality in the Danish general population: a Mendelian randomization study

Meta-analyses have suggested no association between milk intake and mortality. Since only few studies have been conducted, we investigated the association between the lactase persistent genetic variant LCT-13910 C/T (rs4988235), a proxy for long-term low and high intake of milk, and mortality. We used two Danish population-based studies with self-reported intake of milk and genotyping for LCT-13910 C/T. We obtained information on all-cause and cause-specific mortality (cardiovascular and cancer) from the national Danish registries. We used multivariable adjusted Cox regression to assess the association between milk intake and mortality in 74,241 individuals, and both logistic and Cox-regression to assess the association between genetic lactase persistence and mortality in 82,964 individuals using a Mendelian randomization design. We applied per T-allele, co-dominant and dominant models. During a mean follow-up of 7 years, 9759 individuals died, 2166 from cardiovascular disease, and 2822 from cancer. Observationally, there was no association between intake of skimmed milk and all-cause or cardiovascular mortality, and we did not find any associations between intake of semi-skimmed or whole milk with all-cause or cause-specific mortality. Intake of skimmed milk was associated with lower cancer mortality with a hazard ratio of 0.97 (95% CI 0.96–1.00) per doubling in milk intake. Per T-allele, milk intake increased with 0.58 (0.50–0.68) glasses/week. Genetically, we found no associations between the lactase persistent LCT-13910 C/T genotype and all-cause or cause-specific mortality; per T-allele OR (95% CI) for all-cause mortality was 1.02 (0.97–1.06). Our study did not provide strong evidence of observational or genetic associations between milk intake and all-cause or cause-specific mortality.     

外源性乳糖酶对乳糖吸收不良者的干预研究

本研究主要观察有乳糖吸收不良者以外源性乳糖酶补充对乳糖吸收不良和不耐受症状的改善。以２５ｇ乳糖耐量试验筛选出乳糖吸收不良和乳糖不耐受者（出现腹痛、腹泻等胃肠不适症状）作为实验对象,受试者分别服用４００ｍｌ脱脂奶和４００ｍｌ脱脂奶＋乳糖酶９０００ＦＣＣＬＵ,观察４小时内５个小时点呼气中的氢气浓度和不耐受症状。结果显示：外源性乳糖酶干预使受试者乳糖吸收不良发生率由１００％降至４８．９％,不耐受症状发生     

Effectiveness of milk products in dietary management of lactose malabsorption

Eleven lactose malabsorbers were studied to compare the effectiveness of commercially available products recommended for dietary treatment of lactose malabsorption. One product, a commercial lactase preparation, is added to milk for lactose hydrolysis before consumption. The other is a commercial milk product containing lactose-hydrolyzing, nonpathogenic bacteria, Lactobacillus acidophilus. Both of these products are presently recommended for management of lactose malabsorption, although such recommendations have not been validated by controlled studies. Lactose malabsorption was determined by breath H2 analyses after subjects drank four different test doses on 4 different days. The first test dose was 480 ml of low fat milk; the second was 480 ml of milk treated with a commercial lactase preparation; the third was 480 ml of a commercial L. acidophilus-containing milk; and the fourth was 480 ml of the L. acidophilus-containing milk after 1 wk of gastrointestinal exposure to this commercial bacteria-containing milk. The mean breath H2 response to the lactase-treated milk was significantly lower (p less than 0.001) than the mean response to regular milk. However, the mean breath H2 response to either of the test doses of the L. acidophilus-containing milk were not significantly different than responses to regular milk. It is concluded that the lactase-treated milk reduces breath H2 responses and symptomatic discomfort from malabsorption while the L. acidophilus-containing milk does not.     

Lactase activity of Bifidobacterium bifidum

Lactose hydrolase is a small intestinal enzyme which hydrolyzes the carbohydrate lactose from dairy products. During the neonatal period, the enzyme is essential in human nutrition. Later, the specific activity of lactase decreases to low adult levels. In many adult humans, large amounts of lactose from milk can no longer be tolerated. Nevertheless it is now well established that subjects who are lactase non-persistent digest lactose more efficiently from yogurt and fermented milks than from milk. An in vitro assay was used to study the lactase activity of Bifidobacterium bifidum. Frozen cells and fermented milk supplemented with such living organisms were tested. Lactase activity was measured by lactose disappearance. Glucose and galactose by-products from lactose hydrolysis were used differently by the bacterial cells. The optimum pH of lactase is pH = 6.5.     

Lactose and cataract in humans: a review

In this review, the relationship between lactose and human cataract is examined from the presently available biochemical, metabolic, and epidemiological data. The exceptional cases of homozygous enzyme deficiency being excluded, fragmentary data give reason to believe that a risk of cataract secondary to lactose and galactose ingestion is present in certain subpopulations. In these population groups, the size of which is unknown, the lens could be exposed to intermittent episodes of hypergalactosemia due to the presence of a partial enzyme deficiency in the galactose metabolic pathway, and/or the persistence of a high adult jejunal lactase activity, and/or to a large and repeated consumption of either whole lactose or easily absorbed lactose (hydrolyzed forms and nonpasteurized yogurt).     

Dietary determinants of epithelial ovarian cancer: a review of the epidemiologic literature

Ovarian cancer is commonly a fatal disease and, despite advances in screening and treatment, the lack of understanding of the underlying etiology has limited prevention strategies. This article reviews the epidemiologic literature on the relationship between consumption of major food groups and the risk of epithelial ovarian cancer (EOC). We identified 7 cohort studies and 27 case-control studies of consumption of major food groups (fruits and vegetables, meats, eggs, fish, dairy products, grains, fats and oils) and EOC risk. Vegetable but not fruit consumption was found to possibly exhibit beneficial effects on the risk of EOC, whereas high meat consumption may be associated with an increased risk. A protective effect on risk of EOC for whole-grain food consumption as well as for consumption of low-fat milk is suggested by the results of the studies. However, evidence for associations of foods such as fish, grains, milk products, and fats and oils with EOC risk is limited and inconsistent, and further examination of these dietary determinants of EOC are warranted. In conclusion, a typical Western diet, which is high in meats and low in vegetables, may be positively associated with ovarian cancer incidence. However, the association between specific dietary factors and EOC risk remains unclear and merits further examination. In particular, future studies need to address the effect of milk products according to fat content and possible biological mechanisms to explain observed effects.     

Association of galactose-1-phosphate uridyltransferase activity and N314D genotype with the risk of ovarian cancer

Deficiency in the galactose-1-phosphate uridyltransferase (GALT) enzyme results in accumulation of galactose and its metabolites in the ovary (Am J Epidemiol 1989;130:904-10). Galactose may raise gonadotropin levels, resulting in proliferation of ovarian epithelium. In 1993-1999, the authors conducted a population-based case-control study of ovarian cancer in Hawaii and Los Angeles, California, to examine the hypothesis that reduced GALT activity is associated with an increased risk of ovarian cancer. A total of 239 ovarian cancer cases and 244 population controls were interviewed. A blood sample was collected to measure levels of GALT and to assay for the N314D (A940G) polymorphism of the GALT gene. Covariate-adjusted mean GALT activity was similar between cases (23.8 micro mol per hour/g hemoglobin (Hb)) and controls (23.7 micro mol per hour/g Hb) (p = 0.83). No evidence was found for a dose-response relation between the odds ratios for ovarian cancer and GALT activity or the ratio of lactose intake to GALT activity. The risk associated with the presence of at least one variant Asp314 allele was 0.77 (95% confidence interval: 0.42, 1.41). This study did not support the hypothesis that reduced galactose metabolism is a risk factor for ovarian cancer, although increased GALT activity attenuated the inverse association of oral contraceptive pill use with risk.     

Diet and cancer mortality in the counties of Sweden

The association between standardized cancer mortality rate ratios from 1969-1978 and dietary practices was examined in an ecologic study of the 24 counties of Sweden by means of several independent data sources. The study supports the hypothesis that a high intake of cereal fiber protects against colorectal cancer (r = -0.75 for males and r = -0.67 for females). This study found no association between fat intake and colorectal cancer. However, a negative correlation between milk consumption and this type of cancer was found. A suggested hypothesis is that calcium protects against colorectal cancer, since milk is the major source for calcium intake in Sweden. This could indicate that, for societies with a high fat intake, preventive measures which increase the intake of fiber and milk or calcium might have a greater impact on mortality from cancer of the colon and rectum than would a moderate decrease in the intake of fat. There are no indications in this study that fat intake promotes breast cancer.